Abstract: Mal de Debarquement Syndrome (MdDS) is an under-recognized but nevertheless common balance disorder, primarily manifested by constant self-motion sensations consisting of rocking/swaying or gravitational pull of the body, which are accompanied by fatigue, migraine, hypersensitivity to light/noise/crowds, visually induced dizziness, and cognitive dysfunctions. As the name implies (?disembarkation sickness?), in most cases MdDS occurs after exposure to prolonged passive motion, specified as motion-triggered (MT) MdDS. However, the symptoms of MdDS can also occur without a motion trigger, termed as spontaneous MdDS. MdDS is debilitating and entails various mental health issues, such as suicidal thoughts, depression, and anxiety. Treatments for this disorder are still limited, as the specific underlying pathophysiology remains unclear. Recently, our team developed the first treatment method that can safely and effectively ease MdDS symptoms in the majority of patients via readaptation of the vestibulo-ocular reflex (VOR). The hypothesis underlying this treatment is that MdDS is caused by maladaptation of the functional component of the VOR called velocity storage, whose readaptation can be stimulated by exposure to whole-field visual motion coupled with head tilts. Over the past several years, more than 500 patients from around the world have been treated with this method. The success rate immediately after this treatment is 75% for MT MdDS, but some patients report return of symptoms after subsequent flights or prolonged car rides. Thus, the effectiveness of the current MdDS treatment protocol can depend on a serious practical limitation of needing to permanently avoid transportation. Building on the previous hypothesis of velocity storage maladaptation, we currently hypothesize that another method, based on the reduction (habituation) of the velocity storage, can also resolve MdDS symptoms. Velocity storage can be greatly habituated within 4-5 days using a protocol previously developed in our laboratory to reduce susceptibility to motion sickness. Preliminary data support the application of this protocol to MdDS. Moreover, since animal-based research suggests that velocity storage habituation is permanently retained, we further hypothesize that this new treatment method yields robust long-term outcomes. In this project, 30 MT MdDS patients with otherwise normal vestibular and neurological functions will be randomly assigned into two groups, one to be treated by velocity storage habituation and the other by readaptation. Patients will be followed up for 6 months. Based on the preliminary data, we expect both groups to yield similar initial success rates for symptom improvement. However, we expect the group undergoing the habituation protocol to better retain the initial treatment impact in the long term. This project will significantly impact the MdDS treatment practice. The current approach focuses on reducing symptoms, but they can be retriggered by another prolonged exposure to passive motion. The habituation approach on the other hand focuses on permanently minimizing the symptom trigger while also minimizing symptoms. This project will also increase the current understanding of recurrent MdDS.